CHK1_XENLA
ID CHK1_XENLA Reviewed; 474 AA.
AC Q6DE87; Q78CK1; Q78DQ2; Q9YI18;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Serine/threonine-protein kinase Chk1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:11133168, ECO:0000269|PubMed:14767054};
DE AltName: Full=CHK1 checkpoint homolog;
DE AltName: Full=Checkpoint kinase-1;
DE Short=xChk1;
GN Name=chek1; Synonyms=chk1;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PHOSPHORYLATION, AND MUTAGENESIS OF
RP ASN-135.
RX PubMed=9744884; DOI=10.1083/jcb.142.6.1559;
RA Kumagai A., Guo Z., Emami K.H., Wang S.X., Dunphy W.G.;
RT "The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of
RT checkpoint control in cell-free extracts.";
RL J. Cell Biol. 142:1559-1569(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS
RP OF ASP-148.
RC TISSUE=Ovary;
RX PubMed=10068474; DOI=10.1006/dbio.1998.9178;
RA Nakajo N., Oe T., Uto K., Sagata N.;
RT "Involvement of Chk1 kinase in prophase I arrest of Xenopus oocytes.";
RL Dev. Biol. 207:432-444(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND
RP PHOSPHORYLATION.
RX PubMed=10982403; DOI=10.1091/mbc.11.9.3101;
RA Kappas N.C., Savage P., Chen K.C., Walls A.T., Sible J.C.;
RT "Dissection of the XChk1 signaling pathway in Xenopus laevis embryos.";
RL Mol. Biol. Cell 11:3101-3108(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP MUTAGENESIS OF 374-LYS--PHE-380 AND THR-377.
RX PubMed=11150524; DOI=10.1016/s0014-5793(00)02370-x;
RA Wang S.X., Dunphy W.G.;
RT "Activation of Xenopus Chk1 by mutagenesis of threonine-377.";
RL FEBS Lett. 487:277-281(2000).
RN [6]
RP FUNCTION, ACTIVITY REGULATION, AND PHOSPHORYLATION AT THR-314; SER-344;
RP SER-356 AND SER-365.
RX PubMed=11069891; DOI=10.1101/gad.842500;
RA Guo Z., Kumagai A., Wang S.X., Dunphy W.G.;
RT "Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation
RT in response to DNA replication blocks and UV-damaged DNA in Xenopus egg
RT extracts.";
RL Genes Dev. 14:2745-2756(2000).
RN [7]
RP FUNCTION, INTERACTION WITH CLSPN, PHOSPHORYLATION, AND MUTAGENESIS OF
RP ASN-135; THR-314; SER-344; SER-356 AND SER-365.
RX PubMed=11090622; DOI=10.1016/s1097-2765(05)00092-4;
RA Kumagai A., Dunphy W.G.;
RT "Claspin, a novel protein required for the activation of Chk1 during a DNA
RT replication checkpoint response in Xenopus egg extracts.";
RL Mol. Cell 6:839-849(2000).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND
RP AUTOINHIBITION.
RX PubMed=11133168; DOI=10.1006/dbio.2000.9968;
RA Oe T., Nakajo N., Katsuragi Y., Okazaki K., Sagata N.;
RT "Cytoplasmic occurrence of the Chk1/Cdc25 pathway and regulation of Chk1 in
RT Xenopus oocytes.";
RL Dev. Biol. 229:250-261(2001).
RN [9]
RP FUNCTION.
RX PubMed=11251070; DOI=10.1091/mbc.12.3.551;
RA Lee J., Kumagai A., Dunphy W.G.;
RT "Positive regulation of Wee1 by Chk1 and 14-3-3 proteins.";
RL Mol. Biol. Cell 12:551-563(2001).
RN [10]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=12110582; DOI=10.1093/emboj/cdf357;
RA Shimuta K., Nakajo N., Uto K., Hayano Y., Okazaki K., Sagata N.;
RT "Chk1 is activated transiently and targets Cdc25A for degradation at the
RT Xenopus midblastula transition.";
RL EMBO J. 21:3694-3703(2002).
RN [11]
RP DOMAIN FOR INTERACTION WITH CLSPN, PHOSPHORYLATION AT SER-344, AND
RP MUTAGENESIS OF LYS-54; ARG-129; ASN-135; THR-153; ARG-162 AND THR-377.
RX PubMed=12963733; DOI=10.1074/jbc.m304551200;
RA Jeong S.-Y., Kumagai A., Lee J., Dunphy W.G.;
RT "Phosphorylated claspin interacts with a phosphate-binding site in the
RT kinase domain of Chk1 during ATR-mediated activation.";
RL J. Biol. Chem. 278:46782-46788(2003).
RN [12]
RP INTERACTION WITH CLSPN.
RX PubMed=12545175; DOI=10.1038/ncb921;
RA Kumagai A., Dunphy W.G.;
RT "Repeated phosphopeptide motifs in claspin mediate the regulated binding of
RT Chk1.";
RL Nat. Cell Biol. 5:161-165(2003).
RN [13]
RP FUNCTION, DEVELOPMENTAL STAGE, AND PHOSPHORYLATION AT SER-344.
RX PubMed=15296723; DOI=10.1016/j.devcel.2004.07.003;
RA Conn C.W., Lewellyn A.L., Maller J.L.;
RT "The DNA damage checkpoint in embryonic cell cycles is dependent on the
RT DNA-to-cytoplasmic ratio.";
RL Dev. Cell 7:275-281(2004).
RN [14]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=15272308; DOI=10.1038/sj.emboj.7600328;
RA Uto K., Inoue D., Shimuta K., Nakajo N., Sagata N.;
RT "Chk1, but not Chk2, inhibits Cdc25 phosphatases by a novel common
RT mechanism.";
RL EMBO J. 23:3386-3396(2004).
RN [15]
RP INTERACTION WITH CLSPN, AND PHOSPHORYLATION AT SER-344.
RX PubMed=15371427; DOI=10.1074/jbc.m408353200;
RA Kumagai A., Kim S.-M., Dunphy W.G.;
RT "Claspin and the activated form of ATR-ATRIP collaborate in the activation
RT of Chk1.";
RL J. Biol. Chem. 279:49599-49608(2004).
RN [16]
RP SUBCELLULAR LOCATION, DOMAIN AIR, PHOSPHORYLATION AT SER-344, AND
RP MUTAGENESIS OF THR-314; SER-344; SER-356; SER-365; 374-LYS-ARG-375;
RP 451-LYS-ARG-452 AND 456-LYS--LYS-458.
RX PubMed=14767054; DOI=10.1091/mbc.e03-12-0874;
RA Katsuragi Y., Sagata N.;
RT "Regulation of Chk1 kinase by autoinhibition and ATR-mediated
RT phosphorylation.";
RL Mol. Biol. Cell 15:1680-1689(2004).
CC -!- FUNCTION: Serine/threonine-protein kinase which is required for
CC checkpoint-mediated cell cycle arrest and activation of DNA repair in
CC response to the presence of DNA damage or unreplicated DNA. May also
CC negatively regulate cell cycle progression during unperturbed cell
CC cycles. This regulation is achieved by a number of mechanisms that
CC together help to preserve the integrity of the genome. Recognizes the
CC substrate consensus sequence [R-X-X-S/T]. Phosphorylates wee1 at 'Ser-
CC 549' and cdc25c at 'Ser-287', which creates binding sites for 14-3-3
CC proteins which activate wee1 and inhibit cdc25c. Phosphorylates cdc25a
CC at 'Ser-504' which prevents the interaction of cdc25a with CDK2-cyclin
CC E1, CDC2-cyclin A1 and CDC2-cyclin B1. This inhibitory effect does not
CC require 14-3-3 protein binding. Activation of wee1 and inhibition of
CC CDC25 results in increased inhibitory tyrosine phosphorylation of CDK-
CC cyclin complexes and consequent inhibition of cell cycle progression.
CC May promote DNA repair, regulate chromatin assembly and the
CC transcription of genes that regulate cell-cycle progression. May also
CC play a role in replication fork maintenance.
CC {ECO:0000269|PubMed:10068474, ECO:0000269|PubMed:10982403,
CC ECO:0000269|PubMed:11069891, ECO:0000269|PubMed:11090622,
CC ECO:0000269|PubMed:11133168, ECO:0000269|PubMed:11251070,
CC ECO:0000269|PubMed:12110582, ECO:0000269|PubMed:15272308,
CC ECO:0000269|PubMed:15296723, ECO:0000269|PubMed:9744884}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:11133168, ECO:0000269|PubMed:14767054};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:11133168,
CC ECO:0000269|PubMed:14767054};
CC -!- ACTIVITY REGULATION: Activated through phosphorylation by atr or atm in
CC response to DNA damage or inhibition of DNA replication.
CC {ECO:0000250|UniProtKB:O14757}.
CC -!- SUBUNIT: Interacts with and phosphorylates clspn, an adapter protein
CC that regulates the ATR-dependent phosphorylation of chek1.
CC {ECO:0000269|PubMed:11090622, ECO:0000269|PubMed:12545175,
CC ECO:0000269|PubMed:15371427}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11133168,
CC ECO:0000269|PubMed:14767054}. Chromosome
CC {ECO:0000250|UniProtKB:O14757}. Cytoplasm {ECO:0000269|PubMed:11133168,
CC ECO:0000269|PubMed:14767054}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:O14757}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development. Transiently
CC activated by ATR-mediated phosphorylation from the midblastula
CC transition (MBT) to the initial gastrula stage. Developmentally
CC regulated activation of the DNA replication checkpoint may occur as the
CC nucleo-cytoplasmic ratio increases and maternal replication factors are
CC depleted. Elongation of the embryonic cell cycle may allow time for the
CC transcription of genes that initiate the switch from maternal to
CC zygotic control of embryogenesis. {ECO:0000269|PubMed:10068474,
CC ECO:0000269|PubMed:10982403, ECO:0000269|PubMed:12110582,
CC ECO:0000269|PubMed:15272308, ECO:0000269|PubMed:15296723}.
CC -!- DOMAIN: The autoinhibitory region (AIR) binds to the kinase domain and
CC inhibits its activity. {ECO:0000269|PubMed:12963733,
CC ECO:0000269|PubMed:14767054}.
CC -!- PTM: Phosphorylated by atm in response to ionizing irradiation (By
CC similarity). Phosphorylated by atr at Thr-314, Ser-344, Ser-356 and
CC Ser-365 in response to various stimuli that cause checkpoint
CC activation. Phosphorylation impairs binding of the C-terminal
CC autoinhibitory region (AIR) to the kinase domain and thereby enhances
CC kinase activity. {ECO:0000250, ECO:0000269|PubMed:10982403,
CC ECO:0000269|PubMed:11069891, ECO:0000269|PubMed:11090622,
CC ECO:0000269|PubMed:11133168, ECO:0000269|PubMed:12963733,
CC ECO:0000269|PubMed:14767054, ECO:0000269|PubMed:15296723,
CC ECO:0000269|PubMed:15371427, ECO:0000269|PubMed:9744884}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. NIM1 subfamily. {ECO:0000305}.
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DR EMBL; AF053120; AAC64262.1; -; mRNA.
DR EMBL; AB019218; BAA34058.1; -; mRNA.
DR EMBL; AF117816; AAF00098.1; -; mRNA.
DR EMBL; BC077249; AAH77249.1; -; mRNA.
DR RefSeq; NP_001082039.1; NM_001088570.1.
DR AlphaFoldDB; Q6DE87; -.
DR SMR; Q6DE87; -.
DR BioGRID; 99526; 1.
DR iPTMnet; Q6DE87; -.
DR PRIDE; Q6DE87; -.
DR DNASU; 398191; -.
DR GeneID; 398191; -.
DR KEGG; xla:398191; -.
DR CTD; 398191; -.
DR Xenbase; XB-GENE-866102; chek1.S.
DR OrthoDB; 698464at2759; -.
DR BRENDA; 2.7.11.1; 6725.
DR Proteomes; UP000186698; Chromosome 7S.
DR Bgee; 398191; Expressed in ovary and 18 other tissues.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0000794; C:condensed nuclear chromosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035402; F:histone kinase activity (H3-T11 specific); ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; ISS:UniProtKB.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; ISS:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:CACAO.
DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:2000615; P:regulation of histone H3-K9 acetylation; ISS:UniProtKB.
DR GO; GO:0046602; P:regulation of mitotic centrosome separation; ISS:UniProtKB.
DR GO; GO:0010767; P:regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage; ISS:UniProtKB.
DR CDD; cd14069; STKc_Chk1; 1.
DR InterPro; IPR034670; Chk1_catalytic_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Chromosome; Cytoplasm; Cytoskeleton;
KW Developmental protein; DNA damage; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..474
FT /note="Serine/threonine-protein kinase Chk1"
FT /id="PRO_0000085852"
FT DOMAIN 9..265
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..265
FT /note="Interaction with CLSPN"
FT REGION 360..474
FT /note="Autoinhibitory region"
FT REGION 367..474
FT /note="Required for nuclear localization"
FT /evidence="ECO:0000269|PubMed:14767054"
FT ACT_SITE 130
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 15..23
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 38
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 314
FT /note="Phosphothreonine; by ATR"
FT /evidence="ECO:0000269|PubMed:11069891"
FT MOD_RES 344
FT /note="Phosphoserine; by ATR"
FT /evidence="ECO:0000269|PubMed:11069891,
FT ECO:0000269|PubMed:12963733, ECO:0000269|PubMed:14767054,
FT ECO:0000269|PubMed:15296723, ECO:0000269|PubMed:15371427"
FT MOD_RES 356
FT /note="Phosphoserine; by ATR"
FT /evidence="ECO:0000269|PubMed:11069891"
FT MOD_RES 365
FT /note="Phosphoserine; by ATR"
FT /evidence="ECO:0000269|PubMed:11069891"
FT MUTAGEN 54
FT /note="K->A: Abolishes interaction with CLSPN. Abrogates
FT phosphorylation at S-344 and kinase activation during
FT checkpoint signaling."
FT /evidence="ECO:0000269|PubMed:12963733"
FT MUTAGEN 129
FT /note="R->A: Abolishes interaction with CLSPN, abrogates
FT phosphorylation at S-344 and abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:12963733"
FT MUTAGEN 135
FT /note="N->A: Abolishes kinase activity; no effect on
FT interaction with CLSPN."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:12963733, ECO:0000269|PubMed:9744884"
FT MUTAGEN 148
FT /note="D->A: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:10068474"
FT MUTAGEN 153
FT /note="T->A: Abolishes interaction with CLSPN. Abrogates
FT phosphorylation at S-344 and kinase activation during
FT checkpoint signaling."
FT /evidence="ECO:0000269|PubMed:12963733"
FT MUTAGEN 162
FT /note="R->A: Abolishes interaction with CLSPN and kinase
FT activation during checkpoint signaling. No effect on
FT phosphorylation at S-344."
FT /evidence="ECO:0000269|PubMed:12963733"
FT MUTAGEN 314
FT /note="T->A: Abrogates phosphorylation and activation
FT during checkpoint signaling; when associated with A-344; A-
FT 356 and A-365."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 314
FT /note="T->D: Impairs autoinhibition by the AIR domain; when
FT associated with D-344; D-356 and D-365."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 314
FT /note="T->E: Impairs autoinhibition by the AIR domain; when
FT associated with E-344; E-356 and E-365."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 344
FT /note="S->A: Abrogates phosphorylation and activation
FT during checkpoint signaling; when associated with A-314; A-
FT 356 and A-365."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 344
FT /note="S->D: Impairs autoinhibition by the AIR domain; when
FT associated with D-314; D-356 and D-365."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 344
FT /note="S->E: Impairs autoinhibition by the AIR domain; when
FT associated with E-314; E-356 and E-365."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 356
FT /note="S->A: Abrogates phosphorylation and activation
FT during checkpoint signaling; when associated with A-314; A-
FT 344 and A-365."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 356
FT /note="S->D: Impairs autoinhibition by the AIR domain; when
FT associated with D-314; D-344 and D-365."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 356
FT /note="S->E: Impairs autoinhibition by the AIR domain; when
FT associated with E-314; E-344 and E-365."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 365
FT /note="S->A: Abrogates phosphorylation and activation
FT during checkpoint signaling; when associated with A-314; A-
FT 344 and A-356."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 365
FT /note="S->D: Impairs autoinhibition by the AIR domain; when
FT associated with D-314; D-344 and D-356."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 365
FT /note="S->E: Impairs autoinhibition by the AIR domain; when
FT associated with E-314; E-344 and E-356."
FT /evidence="ECO:0000269|PubMed:11090622,
FT ECO:0000269|PubMed:14767054"
FT MUTAGEN 374..380
FT /note="Missing: Induces hyperphosphorylation and enhances
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:11150524"
FT MUTAGEN 374..375
FT /note="KR->AA: Impairs autoinhibition and abrogates nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:14767054"
FT MUTAGEN 377
FT /note="T->A: Induces hyperphosphorylation and enhances
FT kinase activity and cell cycle arrest. Abolishes
FT interaction with CLSPN."
FT /evidence="ECO:0000269|PubMed:11150524,
FT ECO:0000269|PubMed:12963733"
FT MUTAGEN 377
FT /note="T->E: Enhances kinase activity."
FT /evidence="ECO:0000269|PubMed:11150524,
FT ECO:0000269|PubMed:12963733"
FT MUTAGEN 451..452
FT /note="KR->AA: Enhances kinase activity."
FT /evidence="ECO:0000269|PubMed:14767054"
FT MUTAGEN 456..458
FT /note="KIK->AAA: Enhances kinase activity and abrogates
FT nuclear localization."
FT /evidence="ECO:0000269|PubMed:14767054"
FT CONFLICT 165
FT /note="N -> S (in Ref. 1; AAC64262 and 2; BAA34058)"
FT /evidence="ECO:0000305"
FT CONFLICT 230..231
FT /note="Missing (in Ref. 2; BAA34058)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="K -> E (in Ref. 3; AAF00098)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="P -> L (in Ref. 2; BAA34058)"
FT /evidence="ECO:0000305"
FT CONFLICT 243
FT /note="C -> G (in Ref. 1; AAC64262 and 2; BAA34058)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="Missing (in Ref. 3; AAF00098 and 4; AAH77249)"
FT /evidence="ECO:0000305"
FT CONFLICT 331..333
FT /note="YID -> DIN (in Ref. 1; AAC64262 and 2; BAA34058)"
FT /evidence="ECO:0000305"
FT CONFLICT 472..473
FT /note="PD -> SA (in Ref. 1; AAC64262 and 2; BAA34058)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 474 AA; 53975 MW; B6D09B14838F1C0A CRC64;
MAVPFVEDWD LVQTLGEGAY GEVQLAVNRK TEEAVAVKIV DMTRAADCPE NIKKEICINR
MLSHTNIVRF YGHRREGNIQ YLFLEYCRGG ELFDRIEPDV GMPEQDAQKF FQQLIAGVEY
LHSIGITHRD IKPENLLLDE RDQLKISDFG LATVFRHNGK ERLLNKMCGT LPYVAPELIK
SRAFHADPVD VWSCGIVLTA MLAGELPWDQ PNEVCQEYCD WKEKNHYLTP WKKISATPLA
LLCKMLTENP QSRITIPDIK KDRWFTEIIK KGLKRSRVIS GGSSDSSVLC KQIRSDIDIS
HFSHSEEKTA LSSTQPEPRT ALATWDSNSS YIDNLVQGKG ISFSQPACPD NMLLNSQLIG
TPGSSQNVWQ RLVKRMTRFF TKVNAESSYS NLMDTCEKMG YVLKKSCANE VTLSTTDRRN
NKLIFKVNLV EMEDRILLDF RLSKGDGLEF KRHFLKIKKK MDAVVAVQKV LPDT
